The Center for Reproductive Biology Research has served the scientific community for 35 years - first as a P30 Center, then over 10 years as a U54 SCCPIR Grant. The theme chosen and approved for the renewal application is "Mechanisms Regulating Endometrial Function and Dysfunction and Impact on Ovarian Function". The Center's purpose is to establish a comprehensive research and training program to investigate the molecular mechanisms governing female reproduction in mice and humans. Research will be accomplished by four projects: Project I: "Endometrial Steroid Receptor Coregulator-2 in Peri-implantation Biology" will investigate the role of nuclear receptor coregulators in endometrial function. Project II: "Cellular Signals in Ovulation and Luteinization" will investigate the impact of endometrial inflammation on ovarian function. Project III: "MicroRNAs in Endometrial Function and Dysfunction" will identify novel microRNAs altered in endometriosis and investigate their biology. Project IV: "Role of the Orphan Nuclear Receptor COUPTF-II in Endometrial Biology" will determine mechanisms of nuclear receptor and growth factor regulation of endometrial function. Research projects are supported by 4 Cores: Administrative/Bioinformatics Core (A);Animal Core (B);Cell and Tissue Culture Core (C);and Integrated Microscopy Core (D). The Administrative Core will provide the Center with centralized management and centralized data analysis. The Animal Core will centralize the technology and resources required in the use of all in vivo models. The Cell Culture Core will provide investigators with specific reagents for the culture of primary cells and cell lines, as well as the expertise required to manipulate these cells. The Integrated Microscopy Core will aid investigators in the histological, immuno-histochemical and ultrastructural analysis required for the execution of their projects. Finally, the Center will support a Pilot Project to allow exploration of new areas of research, especially those that will translate findings to human clinical research. Thus, this Center for Reproductive Biology Research application will combine basic and translational research approaches to investigate the molecular mechanisms for regulation of female reproduction and fertility in animals and humans and foster the training of investigators in the field of reproductive biology.